The goal of this proposal is to reactivate intensive analysis of the Utah Population Database. This database allows a large scale investigation of the familial component of cancer of all sites in a reference population with almost complete ascertainment of all cancer cases from 1966 to present. A genealogy of approximately l million Utah descendants of the Mormon pioneers originating with their common ancestors has been previously constructed (Skolnick, 1977a; 1980). This collection of Utah families has been computerized and linked into a genealogical database. The genealogy has been linked to a registry of approximately 125,000 Utah Cancer Registry records. We have demonstrated that the Mormons have a typical Northern European gene frequency (McLellan et al., 1984) and normal levels of inbreeding (Jorde and Skolnick, 1981). This population is appropriate for inferences about cancer in populations of Northern European descent. Cancer has been widely studied in this population because of its unique lifestyle characteristics (Lyon et al., 1980a,b; Gardner and Lyon, 1982a,b). Cancer rates in Utah for the years 1966 -1985 are low when compared to the U.S. Third National Cancer Survey (Cancer in Utah 1988). This is largely due to the much lower Utah rates for smoking- associated cancers. Conclusions based upon the study of this population should be applicable to similar populations elsewhere. This project will allow an exhaustive analysis of the familiality of cancer and will benefit from collaborative development of methodology. The database will allow hypotheses to be tested in an unbiased fashion, using population-based samples. This database is unique in its ability to allow testing of such hypotheses. The detailed description of the familial nature of cancer must continue, as it is of fundamental significance for the studies of high incidence families which have become so important in determining a genetic component for many common cancers (Burt et al., 1985, Cannon-Albright et al., 1988; Cannon-Albright et al., 1992; Goldgar et al., 1993). These descriptive studies are a prelude to the detailed genetic and molecular studies which are leading to the isolation and analysis of the genes which predispose to familial cancer.